FBXO2 promotes the progression of papillary thyroid carcinoma through the p53 pathway.

Autor: Guo W; Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Ren Y; Department of Urology, Fenyang Hospital of Shanxi Province, Lüliang, Shanxi, China., Qiu X; Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. fccqiuxg@zzu.edu.cn.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Sep 29; Vol. 14 (1), pp. 22574. Date of Electronic Publication: 2024 Sep 29.
DOI: 10.1038/s41598-024-73455-z
Abstrakt: Emerging evidence have demonstrated that F-box only protein 2 (FBXO2) is intimately associated with malignant tumor development and occurrence. However, neither the functions nor the molecular mechanisms underlying FBXO2 have been determined in the papillary thyroid carcinoma (PTC). The quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry were carried out to detect the FBXO2 expression in PTC tissues. CCK-8 assay, EdU assay and flow cytometry were used to assess cell proliferation, cell cycle and apoptosis. The trans-well assay was conducted to determine the cell invasiveness. The effect of FBXO2 on PTC cell proliferation in vivo was observed through a subcutaneous tumor formation experiment in nude mice. Immunoprecipitation were conducted to detect the interaction between FBXO2 and p53. The ubiquitination assays were conducted to assess the regulation of p53 ubiquitination by FBXO2. FBXO2 was overexpressed in both PTC tissues and cell lines. FBXO2 expression positively correlated with PTC tumor size, lymphatic metastasis, and extramembranous invasion. Furthermore, silencing FBXO2 inhibited PTC cell proliferation and promoted apoptosis. The overexpression of FBXO2 significantly promotes PTC cell proliferation. Mechanistic studies revealed that FBXO2 could directly bind to p53 and promote its ubiquitination degradation. Knockdown of p53 partially reversed the progression arrest induced by FBXO2 Knockdown in PTC cells. FBXO2 knockdown inhibited PTC cell proliferation and promoted apoptosis by targeting p53 for ubiquitination and degradation. This process represents a research foundation for its diagnostic and therapeutic applications.
(© 2024. The Author(s).)
Databáze: MEDLINE
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